The discovery that glutathione peroxidase is a selenoprotein and that 75Se from radioactive selenite is incorporated into the enzyme constitutes evidence that the animal cell genome contains information for a unique assimilatory pathway for selenium. The proposed research will study this pathway in human red blood cells and in human tissue culture cells. Techniques for the rapid assay of 75Se incorporation into glutathione peroxidase will be developed. Experiments will be designed to determine the general pathway of selenite assimilation into the enzyme and to identify the intermediates in selenite assimilation. Selenium in glutathione peroxidase appears to occur in a low molecular weight prosthetic group. This finding suggests that other selenium cofactors might exist with biological and biochemical functions. Experiments will be carried out to study the biosynthesis of selenobiotin and selenothiamine in microorganisms and to determine some properties of the purified selenoanalogs. A survey of plants and microorganisms will be undertaken to see if glutathione peroxidase activity is widespread in nature or restricted to animals.